Epigenetics of trauma

Mental healthAccording to the World Health Organization, mental health ca... More is a fundamental and integral aspect of what we consider global health and overall well-being for each individual. Its core lies in psychological well-being, which can be severely undermined by exposure to trauma, impacting global health even through epigenetic mechanisms.

Trauma, Life, Resilience

Exposure to traumatic events seems to be an intrinsic fate of humanity, since the dawn of time, when our ancestors faced continuous threats to their lives. Even today, most individuals are exposed to some form of traumatic event during their lifetime, including life-threatening situations. The ancestral resilienceAccording to the American Psychological Association, resilie... More capacities of our species allow almost everyone to recover from these events without severe long-term health consequences. However, exposure to traumatic stressFrom a clinical point of view, stress is a physiological and... More has a significant and profound impact at psychological and physiological levels and can be associated with the onset of various disorders. If exposure to traumatic events occurs during physiological and neural development, i.e., at an early age, the effects can be particularly harmful and long-lasting. There can be a progressive worsening of general health conditions, as well as the onset of psychiatric disorders and poor social functioning.

Post-Traumatic Stress Disorder (PTSD)Post-traumatic stress disorder (PTSD) is a complex psycholog... More, Major Depressive Disorder (MDD), and anxietyAnxiety is an emotional response characterized by feelings o... More disorders are among the syndromes triggered by acute or chronic traumatic stress. Fortunately, they affect a smaller percentage of exposed individuals. Indeed, there is a different vulnerability to trauma-induced stress among individuals, partly linked to genetic factors and strongly dependent on the characteristics of the event. Nature, intensity, duration, and repetitiveness of the event clearly play a crucial role in stimulating physiological stress responses, and they do so through epigenetic mechanisms. Epigenetics provides a way by which environmental exposure is “written” onto the genome, as a direct result of genome-environment interaction.

Why is the study of trauma epigenetics important?

Studying the effects of trauma on genome activity and its epigenetic implications serves a dual purpose:

• to deeply understand the molecular mechanisms that characterize stress responses to trauma, to support therapeutic efforts, both pharmacological and psychotherapeutic
• to identify genes, molecules, and mechanisms that may serve as biomarkers of risk or resilience to trauma stress. Many studies now show that all known epigenetic mechanisms are involved in the stress response to trauma, and all undergo alterations in the process. Consequently, the activity of many genes is altered, with downstream effects on biological functions and association with numerous stress-related psychopathologies.

The effect of trauma on the body, physiology, and immune system

At a physiological level, exposure to traumatic events can cause dysfunctions of the HPA axis (hypothalamus-pituitary-adrenal), which plays a key role in the physiological stress response. This hormonal response system, culminating in cortisolThe adrenal glands, small pyramid-shaped glands above the ki... More production, self-regulates when stress levels remain contained. If the stressor is a trauma, the mechanism can strengthen, creating a real short circuit.

This process also affects the immune system, since inflammatory processes are closely linked to control by the HPA axis via cortisol. In this case, pro-inflammatory cytokines are produced, which can influence the central nervous system due to their ability to cross the blood-brain barrier. In this way, the signal originating from the brain at the start of the HPA axis returns to the brain as neuroinflammation and dysregulation of key genes such as COMT and BDNF. The former is involved in the metabolism of molecules like dopamineA neurotransmitter found in the brain and central nervous sy... More and norepinephrine, the latter is one of the most important mediators of neuronal function. These genes, along with all those that are part of the HPA axis and cytokines, are epigenetically regulated through DNA methylation or microRNA activity.

Both in war veterans and in cases of childhood abuse, i.e., individuals with significant traumatic experiences, studies have repeatedly found epigenetic alterations. SerotoninSerotonin, also known as 5-hydroxytryptamine (5-HT), is a ne... More and dopamine transporters, as well as cortisol receptors and pro-inflammatory cytokines, are all involved in association with PTSD, Major Depressive Disorder, and anxiety disorders. For example, a recent study analyzed epigenetic effects in a group of survivors of the World Trade Center disaster (9/11/2001), specifically DNA methylationDNA methylation is one of the most fascinating and, at the s... More. Researchers found significant differences compared to controls in genes involved in synaptic plasticity, cholinergic synapsesA synapse is a term used in neuroscience to describe the fun... More, oxytocinOxytocin is a hormone produced in the brain, specifically in... More activity, and inflammation. The social impact of these pathologies can be significant, given the frequent occurrence of social interaction problems and depressionDepression is a disorder characterized by persistent sadness... More among affected individuals.

Encouragingly, what is “written” on our genome can potentially be erased by developing the right approaches. By nature, the set of epigenetic mechanisms allows reversibility of their effects on genes. Intervening with appropriate treatments, both pharmacological and non-pharmacological, as well as with mindfulness practices, can help rewrite seemingly unsolvable stories.

Fondazione Patrizio Paoletti at Women Minding their Own Business

To raise awareness about the importance of epigenetics, Fondazione Patrizio Paoletti was present on May 7 and 8 at the Women Minding their Own Business conference, an international event promoting the value of equity and inclusive leadership. Fondazione Patrizio Paoletti was represented by Sabrina Venditti, researcher at the Department of Biology and Biotechnology “Charles Darwin” at Sapienza University of Rome.

Sabrina Venditti provided an overview on the epigenetics of violence against women, showing how trauma translates, via epigenetic mechanisms, into alterations in stress response, the immune system, and brain functions. Venditti emphasized that the main goals of epigenetic research in this field today are:

• identify specific epigenetic biomarkers
• promote empathetic and personalized therapeutic approaches
• support holistic well-being of women.

Epigenetics is relevant because, on the one hand, it is reversible and does not change the DNA sequence: the marks can be erased with pharmacological and non-pharmacological means. On the other hand, epigenetics acquires individual and unique characteristics for each person: any type of intervention can be personalized in the healing and resilience process.

Contribution by Sabrina Venditti, researcher at the Department of Biology and Biotechnology “Charles Darwin” at Sapienza University of Rome.